In recent years detectors with very good spatial, energy, and timing resolution, as well as high sensitivity, have been incorporated into commercial PET/CT scanners by each of the major manufacturers. These instruments use detector blocks, or modules that incorporate LSO/LYSO scintillation crystals in a pixelated design, such that the cross-section of the pixel, typically 4 x 4-mm2, determines the spatial resolution. Continuous scintillation detectors using NaI (Tl) were used in PET for many years, but due to its relatively low stopping power and long decay time it could not provide competitive performance compared to LSO/LYSO introduced in PET scanners in the early 2000's. This research proposal seeks to develop a continuous LYSO detector block to take advantage of the favorable properties of this material, but with the advantages of a continuous detector. Compared to a pixelated detector block, we expect a continuous detector to have very uniform light sampling for all interactions within the crystal block, which leads to excellent performance of spatial, energy, and timing resolution. There are also potential cost savings in manufacturing a continuous block detector compared to a pixelated detector, particularly for designs required high spatial resolution. On a system level, a detector with continuous positioning enables improved spatial and angular sampling (without detector motion or wobbling), which leads to improved image reconstruction. Further, a continuous detector design lends itself to measurement of depth-of-interaction (DOI), which can be used to reduce the system parallax error. The key to excellent spatial resolution in a continuous block detector, which is thick enough to achieve high sensitivity, is to control the spread of light from the site of gamma interaction. The signal-to-noise of the measurement of scintillation photons by the photo-detectors, coupled to one surface of the scintillator, is dependent on the light response function (LRF) and determines the resolution of the detector. The focus of this research proposal is to develop and evaluate the methodology to improve the LRF by applying the technology of laser induced optical barriers (LIOB) to our continuous scintillation crystal blocks. It has been demonstrated that LIOBs can be created in LYSO crystals, therefore, the goal of our work is to determine how to utilize this technology to achieve an optimal LRF in a thick, continuous crystal. The combination of continuous position sampling in the transverse direction and DOI information will improve performance for clinical PET. Our specific aims are 1) characterize the behavior of laser induced optical barriers in continuous scintillation crystals, 2) develop a computer model to optimize the light response function in the scintillation crystal so as to improve spatial resolution and enable depth-of-interaction measurements, and 3) test the performance of a continuous scintillation detector with optimized arrangement of laser induced optical barriers.